Association analysis of the ephrin-B2 gene in African-Americans with end-stage renal disease.
Genome scans in African-Americans with end-stage renal disease (ESRD) identified linkage on chromosome 13q33 in the region containing the ephrin-B2 ligand (EFNB2) genes. Interactions between the ephrin-B2 receptor and ephrin-B2 ligand play essential roles in renal angiogenesis, blood vessel maturation, and kidney disease. The EFNB2 gene was evaluated as a positional candidate for non-diabetic and diabetic ESRD susceptibility in 1,071 unrelated African-American subjects; 316 with non-diabetic etiologies of ESRD, 394 with type 2 diabetes-associated ESRD and 361 healthy controls. Single nucleotide polymorphism (SNP) genotyping was performed on the Sequenom Mass Array System. Statistical analyses were computed using Dandelion version 1.26, Snpaddmix version 1.4 and Haploview version 3.32. Twenty-eight HapMap tag SNPs were genotyped spanning the 39 kilobases (kb) of the EFNB2 coding region, with average spacing of 1.43 kb. Analysis of 710 ESRD patient samples and 361 controls provided no evidence of single SNP associations in either diabetic or non-diabetic ESRD; although nominal evidence of association with all-cause ESRD was observed with a two SNP (p = 0.022) and three SNP (p = 0.023) haplotype, both containing SNPs rs7490924 and rs2391335 in intron 1. Although an attractive positional candidate gene, polymorphisms in the EFNB2 gene do not appear to contribute in a substantial way to non-diabetic, diabetic or all-cause ESRD susceptibility in African-Americans. Additional genes within the chromosome 13q33 linkage interval are likely contributors to African-American non-diabetic ESRD.


A novel undecametallic iron(III) cluster with an S = (11)/(2) spin ground state.
The reaction of [NEt(4)](2)[Fe(2)OCl(6)] with sodium benzoate, 4,6-dimethyl-2-hydroxypyrimidine (dmhp), and 1,1,1-tris(hydroxymethyl)ethane (H(3)thme) gives the undecametallic compound [NEt(4)][Fe(11)O(4)(O(2)CPh)(10)(thme)(4)(dmhp)(2)Cl(4)]. X-ray crystallography, EPR spectroscopy, bulk magnetic susceptibility studies, and low-temperature single-crystal magnetic measurements were used to characterize the compound. Magnetic measurements indicate an S = (11)/(2) ground state with the parameters g = 2.03 and D = -0.46 cm(-)(1). Single-crystal magnetic studies show hysteresis of molecular origin at T < 1.2 K with fast quantum mechanical tunneling at zero field.


Arg-265: a critical residue of L.donovani cytosolic SHMT in maintaining the binding of THF and catalysis.
Serine hydroxymethyltransferase belongs to the class of pyridoxal-5-phosphate enzymes along with aspartate aminotransferase. To explore the function of residue(s) involved in binding of the carboxylate group of Tetrahydrofolic acid (THF) to L. donovani cytosolic serine hydroxymethyltransferase (LdcSHMT), the gene was cloned in pET-28(a) vector, overexpressed and purified to homogeneity. With the help of docking results of THF to the active site of protein, the key residues involved in interaction were identified. In an attempt to unravel the function of Arg265 residue involved in binding of the carboxylate group of THF, Arg-265 was mutated to Ala by site-directed mutagenesis. The Arg265Ala-LdcSHMT showed increased Km value (threefold) and decreased kcat/Km value (threefold) for H₄-folate as compared with wild type enzyme. The wild and mutant enzymes exhibited similar Km and kcat/Km values for L-allo-threonine. Unlike the wild type enzyme, mutant failed to form characteristic quinonoid intermediate and was unable to carry out the exchange of α-proton from glycine in the presence of Tetrahydrofolate. These results suggested that Arg265 residue is required for the binding of Tetrahydrofolate and may be the base that abstracts α-proton from glycine, leading to formation of quinonoid intermediate in cytosolic SHMT of L. donovani.


Pain, movement, and mind: does physical activity mediate the relationship between pain and mental health among survivors of breast cancer?
This study examined the relationship between pain and mental health outcomes of depression and affect among survivors of breast cancer. The mediating role of physical activity was also tested. Survivors of breast cancer (N=145) completed self-report measures of pain symptoms at baseline, wore an accelerometer for 7 days, and reported levels of depression symptoms and negative and positive affect 3 months later. Hierarchical linear regression analyses, controlling for personal and cancer-related demographics, were used to test the association between pain symptoms and each mental health outcome, as well as the mediation effect of physical activity. Pain positively predicted depression symptoms [F(6,139)=4.31, P<0.01, R=0.15] and negative affect [F(5,140)=4.17, P<0.01, R=0.13], and negatively predicted positive affect [F(6,139)=2.12, P=0.03, R=0.08]. Physical activity was a significant (P<0.01) partial mediator of the relationship between pain and depression and between pain and positive affect. Participation in physical activity is one pathway through which pain influences mental health. Efforts are needed to help survivors of breast cancer manage pain symptoms and increase their level of physical activity to help improve mental health.


A large inflammatory fibroid polyp in the sigmoid colon treated by endoscopic resection.
Inflammatory fibroid polyp (IFP) is a rare, localized, nonneoplastic lesion originating from the submucosa of the gastrointestinal tract. Microscopically, these lesions are made up of a complex network of variable-size blood vessels and diffuse inflammatory cells contained in the edematous stroma. They are most often found in the stomach, followed by the small intestine, and rarely in the esophagus or the large intestine. We report a case of sigmoid colonic IFP presenting bloody stool treated with endoscopic resection.


A Sensitive Method for Detecting Beauveria bassiana, an Insecticidal Biocontrol Agent, Population Dynamics, and Stability in Different Substrates.
Beauveria bassiana is a well-known insecticidal biocontrol agent. Despite its broad field applications, its survival, colonization, and stability under field conditions remained unclear, mainly due to the lack of a quick and reliable detection method. In this study, we developed a quantitative real-time PCR technology to monitor the stability and population dynamics of B. bassiana in different substrates (water, soil, and on the cotton leaves surface), different spores of B. bassiana applied on Chinese cabbage leaves surface, and the lethality of Pieris rapae spraying with different spores of B. bassiana. Our results showed a decreased concentration of B. bassiana DNA in all three substrates from the 1st day till 9th day of post inoculation (dpi) period, possibly due to the death of B. bassiana. After this decrease, a quick and significant rebound of B. bassiana DNA concentration was observed, starting from the 11th dpi in all three substrates. The B. bassiana DNA concentration reached the plateau at about 13th dpi in water and 17th dpi in the soil. On cotton leaves surface, the B. bassiana DNA concentration reached the highest level at the 17th dpi followed by a small decline and then stabilized. This increase of DNA concentration suggested recovery of B. bassiana growth in all three substrates. We found that the most suitable killing effectiveness of P. rapae was the 1.0 × 107 spores/mL of B. bassiana. In summary, we have established a detection technology that allows a fast and reliable monitoring for the concentration and stability of B. bassiana under different conditions. This technology can benefit and help us in the development of proper management strategies for the application of this biocontrol agent in the field.


A fiber composite laminate endodontic post and core.
The goals of endodontic post and core procedures are to provide maximum retention of the post and resistance to fracture of the roots. Presented is a recently developed fiber composite laminate (FCL) post and core technique which results in a bonded structure that is conservative, morphologic, retentive, versatile, esthetic, and helps resist root fracture. To ascertain the durability of FCL posts and cores, an in vitro pilot study with stress testing is included. The results of the study are compared to other post and core materials to show how well this technique approaches the ideal characteristics for endodontic post and cores.


Inheritance of oral susceptibility of Aedes aegypti to Chikungunya virus.
A colony of rosy eye mutants of Aedes aegypti was established. This strain was refractory to Chikungunya virus by oral route of infection when compared with the wild-type parent strain. The refractoriness of this strain seems to be due to a mesentronal barrier, since both the mosquito strains supported the multiplication of virus after intrathoracic inoculation. The rosy eye strain was also found to be refractory to Sagiyama virus (Alphaviridae: Getah virus subtype) when compared with wild-type parent strain, but no such difference in the oral susceptibility was found with dengue-2 (Flaviviridae) virus. The rosy eye mutant appears to be closely linked to the gene(s) for refractoriness to alpha viruses and may be useful in future studies in understanding the genetic basis of vector competence of Ae. aegypti to arboviruses.


Patient-Specific Considerations, the GABA Pathway, and New Clinical Trial Data on Neuroactive Steroids in MDD and PPD.
Major depressive disorder (MDD) and major depressive episode with peripartum onset, commonly referred to as postpartum depression (PPD), are among the most common psychiatric illnesses and are leading contributors to disability and suicide. Standard of care antidepressants are the cornerstone of MDD treatment; however, nonadherence to antidepressants has been widely recognized as one of the reasons for treatment failure in MDD. Delayed response in current therapies can take up to 4 or even 8 weeks for patients to experience therapeutic benefits. Low treatment response rates are seen in a considerable amount of patients, with early-stage treatment-resistant depression (TRD) affecting 50% of patients receiving first-line treatments and 30% developing into substantive TRD. Given these treatment gaps, there is an urgent need to develop novel antidepressants with a faster onset of action and shorter treatment course, which could improve adherence and treatment response rates. The neurobiology of depression is multifactorial, with different pathways converging on the development of the neurocircuit dysfunction characteristic of depression. Neuroactive steroids play an important role in modulating acute and chronic stress via their phasic and tonic inhibitory effects on select GABAA receptors, ultimately modulating neurocircuit function. With clinical recognition of the importance of neurosteroids in the modulation of GABAA signaling pathways, researchers have developed novel neuroactive steroid-based pharmacotherapies that have been tested in clinical studies. Given their rapid onset of action and shorter treatment course, these novel antidepressants have the potential to change the treatment paradigm for MDD and PPD.


Translation termination reinitiation between open reading frame 1 (ORF1) and ORF2 enables capsid expression in a bovine norovirus without the need for production of viral subgenomic RNA.
A generally accepted view of norovirus replication is that capsid expression requires production of a subgenomic transcript, the presence of capsid often being used as a surrogate marker to indicate the occurrence of viral replication. Using a polymerase II-based baculovirus delivery system, we observed capsid expression following introduction of a full-length genogroup 3 norovirus genome into HepG2 cells. However, capsid expression occurred as a result of a novel translation termination/reinitiation event between the nonstructural-protein and capsid open reading frames, a feature that may be unique to genogroup 3 noroviruses.


Laparoscopic Hernia Repair versus Open Herniotomy in Children: A Controlled Randomized Study.
Background. Laparoscopic hernia repair in infancy and childhood is still debatable. The objective of this study is to compare laparoscopic assisted hernia repair versus open herniotomy as regards operative time, hospital stay, postoperative hydrocele formation, recurrence rate, iatrogenic ascent of the testis, testicular atrophy, and cosmetic results. Patients and Methods. Two hundred and fifty patients with inguinal hernia were randomized into two equal groups. Group A was subjected to laparoscopic inguinal hernia repair. Group B was subjected to open herniotomy. The demographic data were matched between both groups. Assessment of the testicular volume and duplex assessment in preoperative, early, and late postoperative periods were done. Results. All cases were completed successfully without conversion. The mean operative time for group A was 7.6 ± 3.5 minutes, 9.2 ± 4.6 minutes and 11.4 ± 2.7 minutes, for unilateral hernia, unilateral hernia in obese child, and bilateral hernia, respectively. The recurrence rate was 0.8% in group A, whereas in group B the recurrence rate was 2.4%. Conclusion. Laparoscopic hernia repair by RN is an effective line of hernia repair. It resulted in marked reduction of operative time, low rate of recurrence, no testicular atrophy, no iatrogenic ascent of the testis, and excellent cosmetic results.


Propranolol treatment externalizes beta-adrenergic receptors in guinea pig myocardium and prevents further externalization by ischemia.
Purified sarcolemmal and light vesicle (intracellular) fractions of beta-adrenergic receptors were used to examine the effects of propranolol on receptor translocation in guinea pig heart. Guinea pigs were given propranolol (0.15 mg/kg/hr) via minipumps for 7 days and either killed or made ischemic for 1 hour via a coronary ligature. Propranolol treatment led to an externalization of beta-receptors from light vesicle to sarcolemmal fractions. This externalization increased the number of surface beta-adrenergic receptors that were functional, as assessed by isoproterenol-stimulated adenylate cyclase activity. After chronic propranolol treatment, ischemia did not further alter receptor distribution. These results suggest that externalization of beta-adrenergic receptors from a light vesicle fraction to the sarcolemma contributes to up-regulation of beta-receptors that occur in response to both propranolol treatment and ischemia. Because propranolol-treated animals show blunting in externalization after myocardial ischemia, propranolol treatment and myocardial ischemia appear to access the same pool of intracellular beta-adrenergic receptors. Depletion of this pool of receptors along with receptor blockade may thus contribute to the mechanism by which the drug is efficacious in preventing some adverse effects of ischemia.


An aneurysm in the Papyrus of Ebers (108, 3-9).
One of the most ancient descriptions of arterial aneurysm occurs in a paragraph of the Ebers Papyrus: Egyptians considered it a consequence of a vascular lesion and treated it surgically, through an instrument, which had to be previously cauterized on fire.


Short-term transcriptomic analysis at organ scale reveals candidate genes involved in low N responses in NUE-contrasting tomato genotypes.
Understanding the complex regulatory network underlying plant nitrogen (N) responses associated with high Nitrogen Use Efficiency (NUE) is one of the main challenges for sustainable cropping systems. Nitrate (NO3 -), acting as both an N source and a signal molecule, provokes very fast transcriptome reprogramming, allowing plants to adapt to its availability. These changes are genotype- and tissue-specific; thus, the comparison between contrasting genotypes is crucial to uncovering high NUE mechanisms. Here, we compared, for the first time, the spatio-temporal transcriptome changes in both root and shoot of two NUE contrasting tomato genotypes, Regina Ostuni (high-NUE) and UC82 (low-NUE), in response to short-term (within 24 h) low (LN) and high (HN) NO3 - resupply. Using time-series transcriptome data (0, 8, and 24 h), we identified 395 and 482 N-responsive genes differentially expressed (DEGs) between RO and UC82 in shoot and root, respectively. Protein kinase signaling plant hormone signal transduction, and phenylpropanoid biosynthesis were the main enriched metabolic pathways in shoot and root, respectively, and were upregulated in RO compared to UC82. Interestingly, several N transporters belonging to NRT and NPF families, such as NRT2.3, NRT2.4, NPF1.2, and NPF8.3, were found differentially expressed between RO and UC82 genotypes, which might explain the contrasting NUE performances. Transcription factors (TFs) belonging to several families, such as ERF, LOB, GLK, NFYB, ARF, Zinc-finger, and MYB, were differentially expressed between genotypes in response to LN. A complementary Weighted Gene Co-expression Network Analysis (WGCNA) allowed the identification of LN-responsive co-expression modules in RO shoot and root. The regulatory network analysis revealed candidate genes that might have key functions in short-term LN regulation. In particular, an asparagine synthetase (ASNS), a CBL-interacting serine/threonine-protein kinase 1 (CIPK1), a cytokinin riboside 5'-monophosphate phosphoribohydrolase (LOG8), a glycosyltransferase (UGT73C4), and an ERF2 were identified in the shoot, while an LRR receptor-like serine/threonine-protein kinase (FEI1) and two TFs NF-YB5 and LOB37 were identified in the root. Our results revealed potential candidate genes that independently and/or concurrently may regulate short-term low-N response, suggesting a key role played by cytokinin and ROS balancing in early LN regulation mechanisms adopted by the N-use efficient genotype RO.


Metal versus ligand alkylation in the reactivity of the (bis-iminopyridinato)Fe catalyst.
The alkylation of the Brookhart-Gibson {2,6-[2,6-(i-Pr)2PhN=C(CH3)]2(C5H3N)} FeCl2 precatalyst with 2 equiv of LiCH2Si(CH3)3 led to the isolation of several catalytically very active products depending on the reaction conditions. The expected dialkylated species {2,6-[2,6-(i-Pr)2PhN=C(CH3)]2}(C5H3N)Fe(CH2SiMe3)2 (2) was indeed the major component of the reaction mixture. However, other species in which alkylation occurred at the pyridine ring ortho position, {2,6-[2,6-(i-Pr)2PhN=C(CH3)]2-2-CH2SiMe3}(C5H3N)Fe(CH2SiMe3) (1), and at the imine C atom, {2-[2,6-(i-Pr)2PhN=C(CH3)]-6-[2,6-(i-Pr)2PhNC(CH3)(CH2 SiMe3)](C5H3N)}Fe(CH2SiMe3) (3), have also been isolated and fully characterized. In addition, deprotonation of the methyl-imino functions and formation of a new divalent Fe catalyst {[2,6-[2,6-(i-Pr)2PhN-C=(CH2)]2(C5H3N)}Fe(mu-Cl)Li(THF)3 (4) also occurred depending on the reaction conditions. In turn, the formation of 4 might trigger the reductive coupling of two units through the methyl-carbon wings. This process resulted in the one-electron reduction of the metal center, affording a dinuclear Fe(I) alkyl catalyst {[{[2,6-(i-Pr)2C6H5]N=C(CH3)}(C5H3N){[2,6-(i-Pr)26H5]N=CCH2}Fe(CH2SiMe3)]}2 (5). Different from other metal derivatives, complex 5 could not be prepared from the monodeprotonated version of the ligand. Its reaction with a mixture of FeCl2 and RLi afforded instead [{2,6-[2,6-(i-Pr)2PhN-C=(CH2)]2(C5H3N)}FeCH2Si(CH3)3][Li(THF)4] (6) which is also catalytically active. All of these high-spin species have been shown to have high catalytic activity for olefin polymerization, producing polymers of two distinct natures, depending on the formal oxidation state of the metal center.


170 GHz quasi-optical sub-harmonic mixer with a back-to-back lenses packaging based on HDI.
The paper presents a 170 GHz quasi-optical sub-harmonic mixer with a 3D-printed back-to-back lenses packaging. The quasi-optical mixer is comprised by a pair of antiparallel GaAs Schottky diodes, a patch antenna for receiving local oscillator (LO) pump signal, a symmetric-slit patch antenna for receiving radio frequency (RF) signal, dual 3D-printed lenses and a matching network. The quasi-optical mixer with a pair of antiparallel GaAs Schottky diodes is designed on a multilayer build-up printed circuit board (PCB) utilizing commercially low-cost and high-density interconnect (HDI) technology. The LO and RF antennas are placed on the front and back of the multilayer build-up substrate, respectively, thus significantly simplifying the quasi-optical design. Furthermore, dual 3D-printed lenses placed back-to-back are proposed for LO and RF antennas radiation gain enhancement and mechanical robustness. Additionally, the buried planar reflectors in the substrate maintain effective radiation isolation between the antennas. For facilitating coupling efficiency of signal power into the Schottky diodes and signal isolation between the LO pump signal and RF signal, a compact matching network with low-loss quasi-coaxial via transition structure is integrated in the mixer circuit. The measured single-sideband conversion loss is from 11.3 to 15.4 dB in an operation range of 160 to 180 GHz. The measured radiation patterns agree well with the simulated results.


Coordinate tropic hormone regulation of mRNAs for insulin-like growth factor II and the cholesterol side-chain-cleavage enzyme, P450scc [corrected], in human steroidogenic tissues.
Insulin-like growth factors (IGFs) are single-chain polypeptides important for cell proliferation and growth. IGFs are produced in several tissues, suggesting that they function in a paracrine or autocrine fashion as well as functioning as endocrine hormones. We studied the hormonal regulation of IGF-I and IGF-II mRNA in human steroidogenic tissues. In cultured human ovarian granulosa cells, follicle-stimulating hormone, human chorionic gonadotropin, and dibutyryl cAMP increased IGF-II mRNA, but corticotropin [adrenocorticotropic hormone (ACTH)], chorionic somatomammotropin, growth hormone, prolactin, dexamethasone, estradiol, and progesterone had no effect. In cultured human fetal adrenal cells, ACTH and dibutyryl cAMP increased IGF-II mRNA accumulation, but human chorionic gonadotropin and angiotensin II did not. The same five size species of IGF-II mRNA were detected in transfer blots of RNA from granulosa cells and fetal adrenal cells, and all of these increased after hormonal stimuli. Dibutyryl cAMP also increased IGF-II mRNA accumulation in cultured human placental cells. Accumulation of mRNA for the cholesterol side-chain-cleavage monooxygenase [P450scc [corrected]; cholesterol, reduced-adrenal-ferredoxin:oxygen oxidoreductase (side-chain-cleaving), EC 126.96.36.199] was regulated in parallel with IGF-II mRNA in all these steroidogenic tissues. IGF-I mRNA was not detected in transfer blots of these RNAs, and the minimal amounts detected in dot blots showed no detectable change after any of the hormonal stimuli studied. The data indicate that the IGF-II gene is expressed in human steroidogenic tissues and is regulated by cAMP. These data suggest that IGF-II may act in an autocrine or paracrine fashion to stimulate the adrenal and gonadal growth stimulated by ACTH and gonadotropins, respectively.


Psychosocial factors, female fertility and pregnancy: a prospective study--Part II: Pregnancy.
The aim of the study was to determine whether psychosocial factors have an influence on the progress and outcome of pregnancy and whether personality-related or stress factors are significant in this respect. One hundred and ninety-one nulliparas without a history of infertility were prospectively studied gynecologically and psychiatrically. Life changes and changes in stress factors were monitored throughout the study period and obstetric complications were registered. By the end of the study period 120 (63%) of the subjects had given birth, 38 (19%) had abortion, 22 (12%) did not conceive and the remaining 11 (6%) discontinued. Certain psychosocial factors (e.g. life changes, anxiety, subjectively estimated physically and mentally stressful work) were associated with complications of pregnancy. In the logistic regression analysis the psychosocial stress factors were more strongly associated with the outcome of pregnancy than the factors related to personality. Adjusting for the stress-buffering factors (personality, coping methods and social support) did not reduce the original association.


Origin, adaptation and evolutionary pathways of fungal viruses.
Fungal viruses or mycoviruses are widespread in fungi and are believed to be of ancient origin. They have evolved in concert with their hosts and are usually associated with symptomless infections. Mycoviruses are transmitted intracellularly during cell division, sporogenesis and cell fusion, and they lack an extracellular phase to their life cycles. Their natural host ranges are limited to individuals within the same or closely related vegetative compatibility groups. Typically, fungal viruses are isometric particles 25-50 nm in diameter, and possess dsRNA genomes. The best characterized of these belong to the family Totiviridae whose members have simple undivided dsRNA genomes comprised of a coat protein (CP) gene and an RNA dependent RNA polymerase (RDRP) gene. A recently characterized totivirus infecting a filamentous fungus was found to be more closely related to protozoan totiviruses than to yeast totiviruses suggesting these viruses existed prior to the divergence of fungi and protozoa. Although the dsRNA viruses at large are polyphyletic, based on RDRP sequence comparisons, the totiviruses are monophyletic. The theory of a cellular self-replicating mRNA as the origin of totiviruses is attractive because of their apparent ancient origin, the close relationships among their RDRPs, genome simplicity and the ability to use host proteins efficiently. Mycoviruses with bipartite genomes (partitiviruses), like the totiviruses, have simple genomes, but the CP and RDRP genes are on separate dsRNA segments. Because of RDRP sequence similarity, the partitiviruses are probably derived from a totivirus ancestor. The mycoviruses with unencapsidated dsRNA-like genomes (hypoviruses) and those with bacilliform (+) strand RNA genomes (barnaviruses) have more complex genomes and appear to have common ancestry with plant (+) strand RNA viruses in supergroup 1 with potyvirus and sobemovirus lineages, respectively. The La France isometric virus (LIV), an unclassified virus with multipartite dsRNA genome, is associated with a severe die-back disease of the cultivated mushroom. LIV appears to be of recent origin since it differs from its host in codon usage.


Three new potential ovarian cancer biomarkers detected in human urine with equalizer bead technology.
To examine whether urine can be used to measure specific ovarian cancer proteomic profiles and whether one peak alone or in combination with other peaks or CA125 has the sensitivity and specificity to discriminate between ovarian cancer pelvic mass and benign pelvic mass. A total of 209 women were admitted for surgery for pelvic mass at the Gynaecological Department at Rigshospitalet, Copenhagen. Of the women, 156 had benign gynaecological tumors, 13 had borderline tumors and 40 had malignant epithelial ovarian cancer. The prospectively and preoperatively collected urine samples were aliquotted and frozen at -80 degrees until the time of analysis. The urine was fractionated using equalizer bead technology and then analyzed with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Biomarkers were purified and identified using combinations of chromatographic techniques and tandem mass spectrometry. Benign and malignant ovarian cancer cases were compared; 21 significantly different peaks (p<0.001) were visualized using Mann-Whitney analysis, ranging in m/z values from 1,500 to 185,000. The three most significant peaks were purified and identified as fibrinogen alpha fragment (m/z=2570.21), collagen alpha 1 (III) fragment (m/z=2707.32) and fibrinogen beta NT fragment (m/z=4425.09). The area under the receiver operator characteristic curve (ROC AUC) value for these three peaks in combination was 0.88, and their ROC AUC value in combination with CA125 was 0.96. This result supports the feasibility of using urine as a clinical diagnostic medium, and the ROC AUC value for the three most significant peaks in combination with or without CA125 demonstrates the enhanced prediction performance of combined marker analysis.


Neutrophil to Lymphocyte Ratio in Patients with Nonarteritic Anterior Ischemic Optic Neuropathy.
To evaluate the neutrophil to lymphocyte ratio (NLR) in patients with nonarteritic anterior ischemic optic neuropathy (NAION). We investigated 112 subjects comprising 56 patients with NAION and 56 healthy controls at Süleyman Demirel University. Complete blood count, demographic, and clinic data from NAION patients were evaluated in this study. The NLR was calculated in all individuals and compared between the patient and control groups. Cut-off values were also determined. Then, the relationship between NLR and visual outcomes was investigated. The cut-off value for NLR was 1.64. NLR values were significantly higher in NAION patients than in healthy subjects (p < 0.001) and were directly correlated with erythrocyte sedimentation rate levels (r = 0.263, p = 0.006). Also, the NLR value was associated with visual outcomes. Receiver operator characteristic curve analysis revealed a 0.63 area under the curve (confidence interval, 53.7% to 74.1%), 85% sensitivity and 41% specificity at the cut-off NLR value. The NLR may be a biomarker with good sensitivity that is quick, cost effective and easily detected in serum. It can be used in clinical practice to predict a NAION patient's prognosis in terms of visual outcomes.


Sustainable and Elastic Carbon Aerogel by Polydimethylsiloxane Coating for Organic Solvent Absorption and Potential Application for Sensors (Infections, Environmental, Wearable Sensors, etc.).
Carbon aerogel is a promising material in various applications, such as water treatment, insulators, catalysts, and sensors, due to its porosity, low density, conductivity, and good chemical stability. In this study, an inexpensive carbon aerogel was prepared through lyophilization and post-pyrolysis using waste paper. However, carbon aerogel, in the form of short belts, is randomly entangled without a crosslinking agent and has weak mechanical properties, thus limiting its applications, which would otherwise be various. In this paper, a novel strategy is proposed to fabricate a PDMS-coated carbon aerogel (Aerogel@PDMS). Benefiting from microwave heating, precise PDMS coating onto the carbon frame was able to be carried out in a short amount of time. PDMS coating firmly tied the carbon microstructure, maintaining a unique aerogel property without blocking its porous structure. FE-SEM, RAMAN, XPS, and FT-IR were all used to confirm the surface change in PDMS coating. Compressible stability and water contact angle measurement showed that Aerogel@PDMS is a perspective organic solvent absorbent due to its good resilience and its hydrophobicity, and, as a result, its organic solvent absorption capacity and repeated absorption were evaluated, ultimately suggesting a promising material in oil clean-up and pollution remediation in water. Based on our experimental results, we identified elastic carbon aerogels provided by a novel coating technology. In the future, then, the developed carbon/PDMS composite can be examined as a promising option for various applications, such as environmental sensors, virus sensors, and wearable sensors.


Promoting Room Temperature Phosphorescence through Electron Transfer from Carbon Dots to Promethazine.
Room temperature phosphorescence (RTP) as a fascinating phenomenon shows great potential toward multiple applications. Howbeit, it is challengeable to improve the phosphorescence efficiency of carbon dots (CDs) owing to their short lifetime. Herein, we proposed a facile, rapid, and gram-scale strategy to synthesize the cross-linked carbon dots (named N-CDs) with both bright blue fluorescence and green RTP emissions. To be specific, the polymer of polyethylenimine (PEI) served as the cross-linking agent and carbon source, during which process phosphoric acid accelerated the formation of the compact carbon core within 30 s. Subsequently, the cross-linked carbon dots with the rigid network formed a small singlet-triplet energy splitting (ΔEST) of 0.490 eV, thus exhibiting a long RTP lifetime of 429.880 ms while coated on the filter paper through the hydrogen bonds. Taking advantage of the double luminescence, we successfully achieved the dual-channel detection of promethazine by N-CDs. The fluorescence of N-CDs was obviously quenched by promethazine through the electron-transfer process, displaying the linear range from 0.4 to 8 mM. Significantly, the electron transfer (ET) from carbon dots to promethazine boosted their phosphorescence efficiency and prolonged the lifetime to 565.190 ms, and the enhanced phosphorescence facilitated the sensitive recognition of promethazine with the concentration range of 1-3000 μM. Meanwhile, the possible autofluorescence interference from biological samples could be avoided through this RTP assaying mode, providing the more accurate results. Also, their RTP and fluorescence endowed the current N-CDs with the ability of dual-signal painting and imaging. This strategy may broaden the new approaches to produce the long-lifetime and high-efficiency RTP material toward the sensing purpose.


Dalteparin for deep venous thrombosis: a hospital-in-the-home program.
To assess the efficacy, safety and cost savings of home treatment of lower-limb deep venous thrombosis (DVT). A hospital-in-the-home treatment program. One hundred patients with acute lower limb DVT (53 proximal, 47 distal), and no contraindication to home treatment, were entered into the program from March 1995 to February 1997. All patients received dalteparin, 200 units/kg subcutaneously, once daily for a minimum of five days, with commencement of oral anticoagulation (warfarin) on Day 2. Patients with proximal DVT had lung ventilation-perfusion scans performed and were admitted to hospital for at least 24 hours. Patients with distal DVT were discharged directly to home treatment. Clinical responses and the results of sequential duplex ultrasonography at one week, one month, three months and six months. There were no major, but six minor, bleeding complications, two of which led to dalteparin being withdrawn. Sixteen patients had lung ventilation-perfusion scans showing a high probability of pulmonary embolism. All were asymptomatic, and follow-up for at least three months showed no symptomatic thromboembolic events. Duplex ultrasonography showed progression of thrombosis in the first week of therapy in 13.2% of distal and 2.7% of proximal thromboses. Thereafter, distal DVT improved at a much greater rate than proximal DVT; after six months complete resolution was seen in 60.7% of distal and 18.5% of proximal thromboses, respectively. Cost saving was $197 per bed-day equivalent compared with inpatient care. At 15 months' follow-up, swelling and/or pain was reported by 49% of patients with distal DVT and 66% of those with proximal DVT. Once-daily dalteparin therapy for DVT in a hospital-in-the-home setting was safe, efficacious and cost effective. However, DVT resolution is a slow process, with significant long term morbidity.


Plasma cell granuloma associated with pulmonary actinomycosis: a case report.
Plasma cell granuloma (PCG) of the lung is a rare disease that usually presents as a pulmonary nodule or mass on incidental radiographic examination without symptoms. Although the etiology of PCG is still controversial, many findings have lent support to the lesion being a reactive inflammatory process rather than a neoplastic one. We describe a 53-yr-old male who presented with a hemoptysis and have a lung mass at the left upper lobe on chest radiograph. The lung mass was primarily diagnosed as PCG by percutaneous needle aspiration and biopsy, and the patient was treated with oral steroid because he and relatives refused the operation. However, the size of the lung mass did not change and open thoracotomy and lobectomy were done therefore. He was confirmed as having pulmonary actinomycosis with PCG after surgery. To our knowledge, this is the first report of PCG associated with actinomycosis in Korea.


Poorer color discrimination by females when tested with pseudoisochromatic plates containing vanishing designs on neutral backgrounds.
It might be expected that normal trichromatic females would perform as well as normal trichromatic males of the same age when tested with standard clinical color-vision tests that use pseudoisochromatic vanishing designs on neutral gray backgrounds such as the Hardy-Rand-Rittler (HRR) pseudoisochromatic plates and the Neitz Test of Color Vision (NTCV). Here 2966 children aged 6-13 years from four municipalities in Norway were tested in their school classrooms with the NTCV. Children who made errors on the test were retested. 187 males and 152 females made one or more errors on retest, and each was tested individually on the Richmond HRR Fourth Edition. 8% of the males were defined as color deficient when a double criterion for failing was applied, that is, one or more errors on the NTCV and two or more errors on the HRR. The calculated frequency of color-deficient females (homozygotes) for the same criterion is 0.42%. By contrast, 3% of females failed the criterion that gave a stable population of color-deficient males. This result is considered in relation to reports of female carriers of color-vision deficiency having problems with the Ishihara test and of females having poorer color discrimination than males.


Fourth-Year Medical School Course Load and Success as a Medical Intern.
The fourth year of medical school has come under recent scrutiny for its lack of structure, cost- and time-effectiveness, and quality of education it provides. Some have advocated for increasing clinical burden in the fourth year, while others have suggested it be abolished. To assess the relationship between fourth-year course load and success during internship. We reviewed transcripts of 78 internal medicine interns from 2011-2013 and compared the number of intensive courses (defined as subinternships, intensive care, surgical clerkships, and emergency medicine rotations) with multi-source performance evaluations from the internship. We assessed relative risk (RR) and 95% confidence interval (CI) of achieving excellent scores according to the number of intensive courses taken, using generalized estimating equations, adjusting for demographics, US Medical Licensing Examination (USMLE) Step 1 board scores, and other measures of medical school performance. For each additional intensive course taken, the RR of obtaining an excellent score per intensive course was 1.05 (95% CI 1.03-1.07, P < .001), whereas the RR per nonintensive course taken was 0.99 (95% CI 0.98-1.00, P = .03). An association of intensive course work with increased risk of excellent performance was seen across multiple clinical competencies, including medical knowledge (RR 1.08, 95% CI 1.04-1.11); patient care (RR 1.07, 95% CI 1.04-1.10); and practice-based learning (RR 1.05, 95% CI 1.03-1.09). For this single institution's cohort of medical interns, increased exposure to intensive course work during the fourth year of medical school was associated with better clinical evaluations during internship.


Interstitial lung disease associated with systemic sclerosis: what is the evidence for efficacy of cyclophosphamide?
Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis (SSc) that may be responsible for severe restrictive lung disease and represents one of the two main causes of disease-related death in SSc patients. Since 1993, the beneficial effect of oral or intravenous cyclophosphamide (CYC) in the treatment of SSc-related ILD has been reported in retrospective studies, one study showing improvement of pulmonary function test scores and/or chest computed tomography at 1 year and improvement of survival at 16 months. The results of two controlled trials were recently reported. The Scleroderma Lung Study, a prospective randomized placebo-controlled trial, included 158 patients of whom 145 completed at least 6 months of treatment. The course of forced vital capacity (primary outcome) adjusted at 1 year was significantly better in the group treated with oral CYC (P < 0.03), although the effect of CYC was minor. The Fibrosing Alveolitis in Scleroderma Trial (FAST) included 45 patients with SSc-related ILD who were randomized to receive prednisolone (20 mg per day) and 6 CYC infusions (600 mg/m monthly) or placebo. This trial did not demonstrate significant improvement of the primary or secondary endpoints in the active treatment group versus placebo. Since with the exception of the study of Silver et al. none of the patients included in retrospective or prospective studies were selected on the basis of progression of ILD. Since only a minority of SSc patients develops severe ILD, we propose that further studies evaluating CYC should focus on the subgroup of SSc patients with worsening ILD.


Hofmeister effects on poly(NIPAM) microgel particles: macroscopic evidence of ion adsorption and changes in water structure.
The term Hofmeister effects is broadly used to refer to ionic specificities in many different physical, chemical and biological phenomena. The origin of this ionic specificity is sought in two interdependent microscopic sources: 1) the peculiarities of the solvent structure near surfaces and around the ions, and 2) specific ion adsorption-exclusion mechanisms near a surface. In this work, Hofmeister effects on poly(N-isopropylacrylamide) [poly(NIPAM)]-based microgels are examined. Poly(NIPAM) particles are thermally sensitive microgels exhibiting volume-phase transitions with temperature. This temperature-sensitive system seems to be suitable for the independent observation of the two microscopic sources of Hofmeister effects. On the one hand, volume-phase transition, evaluated by photon correlation spectroscopy (PCS), gives information about how the presence of ions changes the water structure around the poly(NIPAM) chains. On the other hand, electrokinetic studies show relevant data about ionic adsorption-exclusion phenomena at the polymer surface.


Insular-associated causal network of structural covariance evaluating progressive gray matter changes in major depressive disorder.
Morphometric studies demonstrated wide-ranging distribution of brain structural abnormalities in major depressive disorder (MDD). This study explored the progressive gray matter volume (GMV) changes pattern of structural network in 108 MDD patients throughout the illness duration by using voxel-based morphometric analysis. The causal structural covariance network method was applied to map the causal effects of GMV alterations between the original source of structural changes and other brain regions as the illness duration prolonged in MDD. This was carried out by utilizing the Granger causality analysis to T1-weighted data ranked based on the disease progression information. With greater illness duration, the GMV reduction was originated from the right insula and progressed to the frontal lobe, and then expanded to the occipital lobe, temporal lobe, dorsal striatum (putamen and caudate) and the cerebellum. Importantly, results revealed that the right insula was the prominent node projecting positive causal influences (i.e., GMV decrease) to frontal lobe, temporal lobe, postcentral gyrus, putamen, and precuneus. While opposite causal effects were detected from the right insula to the angular, parahippocampus, supramarginal gyrus and cerebellum. This work may provide further information and vital evidence showing that MDD is associated with progressive brain structural alterations.


Cloning of environmental genomic fragments as physical markers for monitoring microbial populations in coking wastewater treatment system.
The association between community functional shift and dynamics of genomic DNA composition can be used to identify functionally relevant populations as indicator organisms for systems monitoring. In this work, fingerprinting-based community DNA hybridization was used to monitor community structural dynamics and identify genomic fragments whose abundance shifts were concomitant to changes in COD removal capacity in a reactor. A laboratory-scale anaerobic-anoxic-oxic fixed biofilm system treating coking wastewater was operated with (LR mode) or without effluent recirculation (LNR mode). The contribution to total chemical oxygen demand (COD) removal by the anoxic reactor increased from 4% in LNR mode to 26% in LR mode. Long primer RAPD (randomly amplified polymorphic DNA) community fingerprints of the anoxic reactor also changed most significantly from the one similar to the anaerobic reactor to one similar to the oxic reactor. DNA hybridization revealed one signature band of 2.1 kb shared by the anoxic and oxic reactors in LR, but not LNR mode. Clone library profiling of this band resulted in one predominant 2.1-kb genomic fragment (B3) with no homologous sequences in GenBank. Real-time polymerase chain reaction indicated that copy numbers of B3 in the anoxic reactor under LR mode were 69 times higher than that under LNR mode, concomitant to a significant increase in COD removal capacity in this reactor. The different patterns of distribution of B3 in the laboratory system and a comparable malfunctioning industrial system demonstrated the potential of this genomic fragment as physical markers in systems monitoring. In addition, this genomic fragment may allow sequence-guided isolation of the host microbe.


Misplaced batteries result in lead poisoning in suckler cows.
Lead poisoning in suckler herdsBovine abortion associated with spoiled or contaminated feedListerial meningoencephalitis in ewesProliferative haemorrhagic enteropathy in pigsPoxvirus infection in a bantam These are among matters discussed in the disease surveillance report for February 2016 from SAC Consulting: Veterinary Services (SAC C VS).


Evaluation of synergistic activity of bovine lactoferricin with antibiotics in corneal infection.
The objectives of this study were to determine whether a synergistic effect could be obtained in vitro between bovine lactoferricin (B-LFcin) and antibiotics against Pseudomonas aeruginosa and Staphylococcus aureus isolates from ocular infections, and to evaluate the use of B-LFcin as an adjunct to the antibiotic treatment of corneal infection in vivo. Chequerboard and time-kill assays were performed to investigate the combined effects of B-LFcin and conventional antibiotics, including ciprofloxacin, ceftazidime and gentamicin, against 17 strains of P. aeruginosa (8) and S. aureus (9) isolated from ocular infection and inflammation, and 1 reference strain of S. aureus. Corneas of C57BL/6 mice were topically challenged with a multidrug-resistant strain of P. aeruginosa. Nine hours post-challenge, mice were treated topically and hourly with either vehicle, B-LFcin, ciprofloxacin or ciprofloxacin containing B-LFcin for 8 h. Corneas were then clinically examined, and bacterial numbers and levels of myeloperoxidase (MPO) evaluated. Synergy between B-LFcin and ciprofloxacin or ceftazidime was identified in most P. aeruginosa isolates, including multidrug-resistant strains, whereas no synergistic effect was seen between B-LFcin and gentamicin. Synergy was only observed with B-LFcin and ciprofloxacin against 2/10 S. aureus strains, and there was no synergy between B-LFcin and any of the other antibiotics tested. Combined B-LFcin and ciprofloxacin treatment significantly improved the clinical outcome, and reduced bacterial numbers and MPO in infected mouse corneas. B-LFcin alone was also able to reduce levels of MPO in infected corneas. These findings indicate that B-LFcin may have advantages as an adjunct therapy with both antimicrobial and anti-inflammatory properties in the treatment of corneal infection.


Association between city-wide lockdown and COVID-19 hospitalization rates in multigenerational households in New York City.
City-wide lockdowns and school closures have demonstrably impacted COVID-19 transmission. However, simulation studies have suggested an increased risk of COVID-19 related morbidity for older individuals inoculated by house-bound children. This study examines whether the March 2020 lockdown in New York City (NYC) was associated with higher COVID-19 hospitalization rates in neighborhoods with larger proportions of multigenerational households. We obtained daily age-segmented COVID-19 hospitalization counts in each of 166 ZIP code tabulation areas (ZCTAs) in NYC. Using Bayesian Poisson regression models that account for spatiotemporal dependencies between ZCTAs, as well as socioeconomic risk factors, we conducted a difference-in-differences study amongst ZCTA-level hospitalization rates from February 23 to May 2, 2020. We compared ZCTAs in the lowest quartile of multigenerational housing to other quartiles before and after the lockdown. Among individuals over 55 years, the lockdown was associated with higher COVID-19 hospitalization rates in ZCTAs with more multigenerational households. The greatest difference occurred three weeks after lockdown: Q2 vs. Q1: 54% increase (95% Bayesian credible intervals: 22-96%); Q3 vs. Q1: 48% (17-89%); Q4 vs. Q1: 66% (30-211%). After accounting for pandemic-related population shifts, a significant difference was observed only in Q4 ZCTAs: 37% (7-76%). By increasing house-bound mixing across older and younger age groups, city-wide lockdown mandates imposed during the growth of COVID-19 cases may have inadvertently, but transiently, contributed to increased transmission in multigenerational households.


Hemolysis as a potential complication of acetaminophen overdose in a patient with glucose-6-phosphate dehydrogenase deficiency.
A 21-year-old Chinese man who took an overdose of acetaminophen was hospitalized. His medical history was significant for glucose-6-phosphate dehydrogenase (G6PD) deficiency. On admission, physical examination was unremarkable and laboratory results were within normal limits. During his hospitalization, the patient experienced a decrease in hemoglobin concentration of almost 4 g/dl and an increase in unconjugated bilirubin consistent with the development of hemolysis. Acetaminophen was the most likely cause of the hemolysis. Clinicians must be aware of this potential complication after acetaminophen overdose in G6PD-deficient patients.


Advances in curcumin-loaded nanopreparations: improving bioavailability and overcoming inherent drawbacks.
Curcumin (CUR), one of the major extracts of turmeric, has gained extensive attention owing to its extraordinary benefits as anti-cancer, anti-bacterial, anti-ulcerative, anti-depressant, anti-inflammatory and wound healing agent. However, a major barrier in its application lies in its inherent nature of low water solubility, instability, and short half-life. Different strategies have been adopted to overcome these barriers like preparing nano-sized formulations and exploiting stable and hydrophilic derivatives, and collaborative drug delivery. Nanopreparations could maintain the pharmacological effect of drugs, even the holistic effects of drug extracts. In addition, nanopreparations based on novel materials make it a reality to regulate the drug release rate according to the various environmental conditions. The therapeutic applications and novel investigated nanopreparations of CUR for prevention and treatment of various diseases, especially, cancer and inflammatory disorders are discussed in this review.


The why, when, where, how, and so what of so-called rapidly acting antidepressants.
Developing antidepressants that are not only more effective but are rapidly acting is the Holy Grail for psychiatry. We review multiple issues that arise in determining rapid responses in antidepressant trials. The current status of purportedly rapid acting agents is first reviewed. Then, a number of key questions/issues are addressed: Is there a unifying definition for rapid response across studies? Should rapid response criteria be based on required measurable effects on overall improvement? On specific symptoms such as psychomotor retardation, depressed mood, or anhedonia? In associated symptoms such as anxiety or insomnia? When should onset be considered rapid-by Day 3? Day7? Day 14? If there is a rapid response, for how long should the effects be maintained? Is maintenance of effect dependent on continuing the medication? Is rapid response associated with specific mechanisms of action? Do the mechanisms of action suggest possible risk for drug abuse? How important is rapid response really in an often chronic or recurrent depressive disorder? In which types of patients could rapid response be particularly important? What are the study design issues that need to be considered for assessing rapid response, including: selection of specific types of depressed patients, multiple doses of drug studied, designation of primary and secondary outcome measures, specific time points at which to determine efficacy, requirements for demonstrating durability, etc. A framework for approaching this complex area is developed for both researchers and clinicians.


[Atrial fibrillation in patients with obstructive hypertrophic cardiomyopathy: clinical characteristics and risk factors].
Objective: To evaluate the clinical characteristics and risk factors for atrial fibrillation(AF)in patients with obstructive hypertrophic cardiomyopathy(OHCM). Methods: Patients with OHCM hospitalized in Fuwai Hospital from March 2011 to January 2016 were enrolled in the present study. Each patient underwent examinations including transthoracic echocardiography, body surface electrocardiograph or dynamic electrocardiogram (Holter). Cardiac troponin I (cTNI) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP)levels were tested and clinical profiles were collected.The subjects were divided into two groups (the AF group and non-AF group). Risk factors for AF in patients with OHCM were assessed by multivariate logistic regression analysis. Results: A total of 309 patients were evaluated in the study. Among them, 17.5%( 54/309) patients were with AF.Age[(51.2±10.1)years vs (43.1 ± 14.4)years], New York Heart Association class(NYHA class)(2.8±0.5 vs 2.6±0.6), disease duration[6.0(4.0, 10.0)years vs 3.0(1.0, 6.0)years], left atrial (LA) dimension[(45.1±7.0)mm vs(42.6 ± 7.4)mm]and NT-pro-BNP levels[2 007(1 565, 3 199)pmol/L vs 1 509(729, 2 921)pmol/L]in the AF group were significantly higher than those in the non-AF group (all P<0.05). Multivariate logistic regression analysis indicated that advanced age(OR=1.04, 95% CI 1.01-1.08, P<0.01), higher NYHA class(OR=2.00, 95% CI 1.08-3.70, P<0.05)and longer disease duration(OR=1.08, 95% CI 1.01-1.15, P<0.05)were independent risk factors for AF in patients with OHCM, in which advanced age(OR=1.05, 95% CI 1.02-1.09, P<0.01), higher NYHA class(OR=3.39, 95% CI 1.53-7.54, P<0.01), LA dimension(OR=1.06, 95% CI 1.01-1.12, P<0.05)and longer clinical course(OR=1.12, 95% CI 1.04-1.20, P<0.01)were associated with AF in male patients, and advanced age (OR=1.05, 95% CI 1.01-1.09, P<0.05)and longer disease duration(OR=1.14, 95% CI 1.01-1.28, P<0.01)were associated with AF in female patients when stratified by gender. Conclusion: Advanced age , higher NYHA class and longer clinical duration are independent risk factors for AF in OHCM patients.


Development of Snake Fungal Disease after Experimental Challenge with Ophidiomyces ophiodiicola in Cottonmouths (Agkistrodon piscivorous).
Snake fungal disease (SFD) is a clinical syndrome associated with dermatitis, myositis, osteomyelitis, and pneumonia in several species of free-ranging snakes in the US. The causative agent has been suggested as Ophidiomyces ophiodiicola, but other agents may contribute to the syndrome and the pathogenesis is not understood. To understand the role of O. ophiodiicola in SFD, a cottonmouth snake model of SFD was designed. Five cottonmouths (Agkistrodon piscivorous) were experimentally challenged by nasolabial pit inoculation with a pure culture of O. ophiodiicola. Development of skin lesions or facial swelling at the site of inoculation was observed in all snakes. Twice weekly swabs of the inoculation site revealed variable presence of O. ophiodiicola DNA by qPCR in all five inoculated snakes for 3 to 58 days post-inoculation; nasolabial flushes were not a useful sampling method for detection. Inoculated snakes had a 40% mortality rate. All inoculated snakes had microscopic lesions unilaterally on the side of the swabbed nasolabial pit, including erosions to ulcerations and heterophilic dermatitis. All signs were consistent with SFD; however, the severity of lesions varied in individual snakes, and fungal hyphae were only observed in 3 of 5 inoculated snakes. These three snakes correlated with post-mortem tissue qPCR evidence of O. ophiodiicola. The findings of this study conclude that O. ophiodiicola inoculation in a cottonmouth snake model leads to disease similar to SFD, although lesion severity and the fungal load are quite variable within the model. Future studies may utilize this model to further understand the pathogenesis of this disease and develop management strategies that mitigate disease effects, but investigation of other models with less variability may be warranted.


Mattering and parental presence in systemic therapy using nonviolent resistance: The utilization of imaginary methods.
An empowered sense of "self" is crucial for emotional well-being and positive relationships. Certain family interaction patterns can disrupt the adult's sense of "mattering" to the child, eroding their perceived self-efficacy. Mattering can be understood as a felt sense of relational agency which is necessary for experiencing one's interactions as meaningful, effective, and self-determined. When parents generate more positive future narratives in co-creation with their therapist, their sense of relevance to a child can be restored. In this way, more constructive forms of interaction can emerge with their child which has hitherto eschewed their care. This article aims to provide a conceptual basis for addressing an absence of reciprocity, where children demonstrate harmful or self-destructive behavior and refuse to cooperate in therapy. In such instances, one-sided parental action, utilizing nonviolent resistance methods, can influence relational dynamics. Imaginary methods can then facilitate shifts to psychological states in which the parent internally experiences efficacy and mattering more often without requiring validation from the "physical child" in the here and now. We introduce examples of specific imaginary techniques, which in our clinical practice have shown to facilitate such shifts in parents. We discuss neuroscientific theories that may account for their powerful impact we witness in our clinical experience.


Sympathoadrenal mechanisms underlying cardiovascular responses to intrathecal substance P in conscious rats.
The sympathoadrenal mechanisms underlying cardiovascular responses to intrathecal (i.th.) injection of substance P (SP), at the T-9 spinal level, were investigated in conscious rats. Release of norepinephrine (NE), and epinephrine (EPI) could be induced by 6.5, 16.25, and 32.5 nmol SP correlated with a pressor and a positive chronotropic response. Release of neuropeptide Y (NPY) was evoked also by 32.5 nmol SP, and released NPY appears to derive from the adrenal medulla. The initial pressor response in intact rats is mediated by NE from sympathetic fibers, whereas the latent pressor response, observed in sympathectomized rats, is possibly due to NPY from the adrenal medulla. Although a functional balance between the sympathetic fibers and the adrenal glands is supported by the results, it appears that only the tachycardia can be efficiently produced by the adrenals in the absence of the sympathetic fibers. This study supports a functional role for SP in regulation of the sympathoadrenal system at the spinal level.


Magnetic resonance spectroscopic studies of pediatric mood disorders: a selective review.
This review article presents a summary of the recent magnetic resonance spectroscopic studies of pediatric mood disorders. Magnetic resonance imaging is a promising tool for investigating the biologic substrates of neuropsychiatric disorders without the use of ionizing radiation. This novel technique has been recently applied to pediatric patients with mood disorders. Structural, chemical, and functional abnormalities in pediatric patients with mood disorders have been reported. To date, only modest numbers of pediatric studies using magnetic resonance imaging have been conducted. Most of these studies have small sample sizes and heterogeneous subject groups. These studies have provided important information regarding the underlying neuro-circuitry and pathophysiology of these complex and disabling disorders, however.


A partial agonist at strychnine-insensitive glycine sites facilitates spatial learning in aged rats.
1-Aminocyclopropanecarboxylic acid (ACPC) is a high affinity ligand at strychnine-insensitive glycine sites of the N-methyl-D-aspartate (NMDA) channels and exhibits partial agonist properties in both biochemical and electrophysiological measures. While ACPC was reported active in animal models used to evaluate potential antidepressants and anxiolytics, its effects on learning and memory are unknown. In the present study we investigated the effects of ACPC on spatial learning in the Morris water maze. On a schedule of 12 learning trials, one trial per day, mature male Wistar rats (3 months of age) rapidly acquired the task. Electroconvulsive shocks applied after each of the learning trials markedly inhibited the consolidation of spatial memory. Administration of either a muscarinic agonist, arecoline (1 mg/kg) or ACPC (250 or 400 mg/kg) 20 min before each of the learning trials did not affect the acquisition of spatial learning. Aged (16 months old) male Wistar rats demonstrated difficulties in the acquisition of spatial learning task. In these subjects, ACPC administered 20 min before each of the learning trials at a dose of 400, but not 250 mg/kg, facilitated the acquisition of spatial memory as indicated on trials 3-5. ACPC did not affect the strength of spatial memory as assessed at the end of conditioning, by measuring swimming behavior of rats in the pool with platform removed. It is suggested that ACPC may alleviate learning deficits observed in the elderly.


An investigation on endoscopic laryngopharyngeal surgery and related outcomes.
Robotic surgery is used in Europe and the US for oropharyngeal/hypopharyngeal cancers. Although robots can successfully perform procedures that are too delicate for surgeons and quickly learn accurate techniques, robotic surgery is not still authorized for the craniocervical region in Japan. In Japan, endoscopic laryngopharyngeal surgery (ELPS) is widely performed. Because oropharyngeal/hypopharyngeal cancer can be resected at an early stage, we have contributed to an improvement in the survival rate. To analyze clinical outcomes and risk factors of postoperative cervical lymph node metastases after ELPS. Fifty-two patients with 71 superficial oropharyngeal/hypopharyngeal cancers were included. A Sato-type arcuation laryngoscope was inserted, and oropharyngeal and hypopharyngeal fields were secured. We have recently been performing head and neck surgery using only a flexible endoscope because gastroscopy and arcuation-type forceps interfere with each other. The 5-year survival rate was 95.2%. The risk factors of lymph node metastases were examined. The depth of the tumor significantly affected lymph node metastases. With a favorable 5-year survival rate and low functional impairment, ELPS is an extremely effective form of treatment. It can provide a clear field of view in the hypopharynx and has a low cost; hence, it should be further developed as a treatment method.


Bexarotene improves motor function after spinal cord injury in mice.
Spinal cord injury is a challenge in orthopedics because it causes irreversible damage to the central nervous system. Therefore, early treatment to prevent lesion expansion is crucial for the management of patients with spinal cord injury. Bexarotene, a type of retinoid, exerts therapeutic effects on patients with cutaneous T-cell lymphoma and Parkinson's disease. Bexarotene has been proven to promote autophagy, but it has not been used in the treatment of spinal cord injury. To investigate the effects of bexarotene on spinal cord injury, we established a mouse model of T11-T12 spinal cord contusion and performed daily intraperitoneal injection of bexarotene for 5 consecutive days. We found that bexarotene effectively reduced the deposition of collagen and the number of pathological neurons in the injured spinal cord, increased the number of synapses of nerve cells, reduced oxidative stress, inhibited pyroptosis, promoted the recovery of motor function, and reduced death. Inhibition of autophagy with 3-methyladenine reversed the effects of bexarotene on spinal cord injury. Bexarotene enhanced the nuclear translocation of transcription factor E3, which further activated AMP-activated protein kinase-S-phase kinase-associated protein 2-coactivator-associated arginine methyltransferase 1 and AMP-activated protein kinase-mammalian target of rapamycin signaling pathways. Intravenous injection of transcription factor E3 shRNA or intraperitoneal injection of compound C, an AMP-activated protein kinase blocker, inhibited the effects of bexarotene. These findings suggest that bexarotene regulates nuclear translocation of transcription factor E3 through the AMP-activated protein kinase-S-phase kinase-associated protein 2-coactivator-associated arginine methyltransferase 1 and AMP-activated protein kinase-mammalian target of rapamycin signal pathways, promotes autophagy, decreases reactive oxygen species level, inhibits pyroptosis, and improves motor function after spinal cord injury.


Electron cooling of high-energy protons in a multiring trap with a tank circuit monitoring the electron-plasma oscillations.
Electron cooling of energetic protons in a multiring trap was investigated experimentally with a tank circuit monitoring electron-plasma oscillations in the trap. The energy of protons was determined by time-of-flight measurements. It is found that a simple model can explain the qualitative behavior of both electron and proton energy when the initial energy of protons is less than 2 keV. Monitoring the electron-plasma temperature with a tank circuit can be an effective tool when energetic particles are electron cooled in a multiring trap.


Differential labelling of bulk endocytosis in nerve terminals by FM dyes.
Bulk endocytosis is triggered in central nerve terminals during intense physiological stimulation. This endocytosis pathway can be labelled by the dye FM1-43 but not its more hydrophilic counterpart FM2-10. This selective labelling was proposed to be due to the retention of FM1-43, but not FM2-10, in slowly retrieving structures after washout of the dye. However, this explanation assumed that bulk endocytosis was a slow process that persisted after stimulation. We have recently shown that the great majority of bulk endocytosis occurs during stimulation, therefore another explanation for the specific labelling of this pathway by FM1-43 must be found. In this paper we show that the ability of FM dyes to label bulk endocytosis is dependent on the concentration of dye used and not their washout properties. When the loading concentration of FM1-43 was reduced 10-fold, its ability to label bulk endocytosis was lost. Conversely when the loading concentration of FM2-10 was increased 10-fold, it now labelled the pathway. This suggests that a difference in affinity of bulk endosome membranes for FM1-43 and FM2-10 underlies the disparity in labelling.


Rare co-inherited alpha-thalassemia minor and beta-thalassemia minor with heterozygous H63D mutation mistaken as iron deficiency anemia: a case report.
The coexistence of alpha- and beta-thalassemia is not uncommon and neither is a single thalassemia subtype with a hemochromatosis H63D mutation, however the inheritance of all three diseases together has yet to be reported. We present this rare case of co-inherited alpha-thalassemia minor and beta-thalassemia minor initially misdiagnosed as iron deficiency anemia (IDA) in a reproductive aged female with a heterozygous H63D mutation. In our case report, a 27-year-old, Asian female presented with excessive lethargy and fatigue for the past 10 months. A year ago, she was prescribed Ferrous Sulfate 325 mg daily supplementation due to a suspicion of IDA secondary to a history of heavy menstruations. Although her reports displayed a low mean corpuscular volume (MCV) anemia, the patient declined therapy at that time due to abnormal labs, specifically regarding her urine and liver that subsequently lead to a hemochromatosis, heterozygous H63D diagnosis following genetic testing. Subsequently, the patient's anemia presenting in the setting of normal ferritin, high iron saturation, and elevated A2 fraction was most likely in accordance to carrying the alpha-thalassemia minor, beta-thalassemia minor, and heterozygous H63D gene mutations. Genetic testing further clarified two of the four alpha-globin genes were deleted, alpha3.7 and alpha4.2, consistent with alpha-thalassemia trait and a heterozygous, frameshift mutation of c.27dupG on the hemoglobin subunit beta (HBB) gene associated with beta-thalassemia minor. The initial diagnosis of IDA was inaccurate following the iron studies displaying normal ferritin levels. This is the first report of combined alpha- and beta-thalassemia with a hemochromatosis H63D mutation. Although the clinical presentation of our patient and laboratory values are stable, the course of inheriting all three diseases together is unknown and may inflate the risk of future complications beyond reported studies. Frequent monitorization of hemoglobin and iron studies will be conducted to follow this rare presentation and prevent life-threating iron overload.


A systematic review of gamification in e-Health.
Gamification is a relatively new trend that focuses on applying game mechanics to non-game contexts in order to engage audiences and to inject a little fun into mundane activities besides generating motivational and cognitive benefits. While many fields such as Business, Marketing and e-Learning have taken advantage of the potential of gamification, the digital healthcare domain has also started to exploit this emerging trend. This paper aims to summarize the current knowledge regarding gamified e-Health applications. A systematic literature review was therefore conducted to explore the various gamification strategies employed in e-Health and to address the benefits and the pitfalls of this emerging discipline. A total of 46 studies from multiple sources were then considered and thoroughly investigated. The results show that the majority of the papers selected reported gamification and serious gaming in health and wellness contexts related specifically to chronic disease rehabilitation, physical activity and mental health. Although gamification in e-Health has attracted a great deal of attention during the last few years, there is still a dearth of valid empirical evidence in this field. Moreover, most of the e-Health applications and serious games investigated have been proven to yield solely short-term engagement through extrinsic rewards. For gamification to reach its full potential, it is therefore necessary to build e-Health solutions on well-founded theories that exploit the core experience and psychological effects of game mechanics.


[Oral gentic syndromes causing dental anomalies].
The author briefly described those genetic syndromes that are accompanied by tooth or dental arch anomalies. Some of these can be corrected by prosthetic means. These anomalies can be indications for prosthetic treatment.


The cytology of the human peritoneal fluid.
A series of 19 human peritoneal fluids obtained by aspiration at laparoscopy and cul-de-sac punctures were analysed for their cellular content. Four types of cells were differentiated: macrophages, mesothelial cells, lymphocytes and polymorphonuclear leukocytes. The macrophages and mesothelial cells represented the two major types of cells, each group constituiting about 36 per cent of the population, while the lymphocytes and polymorphonuclears represented 18 and 7 per cent of the population, respectively. Macrophages were identified by their capacity to engulf alcohol-killed Staphylococcus albus. It appears that by this method of macrophage identification, a more accurate representation of the cellular content of peritoneal fluid can be obtained.


In vivo identification of sialic acid as the ocular receptor for Pseudomonas aeruginosa.
In vivo bacterial adherence of Pseudomonas aeruginosa to the immature ocular epithelium was mediated by a sialic (N-acetylneuraminic) acid (NANA) receptor. Saturation of binding sites on the bacterial surface by NANA prevented attachment of the organism to the epithelial cell membrane receptor. Additionally, a significant number of animals receiving NANA-treated organisms were protected from septicemia and death. In vivo protection studies showed excellent correlation with scanning electron microscopy, in that the number of adherent organisms at the corneal surface decreased dramatically in the presence of NANA. These studies exhibit a strong correlation with clinical cases of human infant ocular infection.


Studies on certain drug-metabolizing enzymes in deoxypyridoxine-treated rats.
The effect of deoxypyridoxine on the activities of drug-metabolizing enzymes was investigated in male rats. Phenylbutazone oxidase and aminopyrine N-demethylase decreased in both liver and kidney of deoxypyridoxine-treated rats that received either an 18% or 8% casein diet. However, the magnitude of decrease in activities was more when the rats received an 8% casein diet. The NADPH oxidase activity remained unchanged following deoxypyridoxine treatment. The diminished activities of phenylbutazone oxidase and aminopyrine N-demethylase noted after deoxypyridoxine treatment were restored by pyridoxine supplementation. The decreased activities of drug-metabolizing enzymes in deoxypyridoxine treated rats were not reversed by thyroxine supplementation. It is suggested that pyridoxine in the form of pyridoxal phosphate might be involved in the regulation of drug-metabolizing activities.


Interaction of carp growth hormone-releasing factor and somatostatin on in vitro release of growth hormone in rainbow trout (Oncorhynchus mykiss).
Possible antagonism between somatostatin (SS) and carp growth hormone-releasing factor (GRF) on growth hormone (GH) secretion was examined by radioimmunoassay in a dispersed rainbow trout pituitary cell culture system. SS (3 nM) significantly antagonized carp GRF(1-29; 1 nM, 10 nM)-induced GH secretion. The slope of the dose-response curve for carp GRF(1-29) with SS was statistically different from that of carp GRF(1-29) alone (p less than 0.05) suggesting a noncompetitive antagonism of SS to carp GRF. The carp GRF(1-29) was also indicated to be a noncompetitive antagonist to SS (p = 0.056). Carp GRF(1-29; 100 nM) was unable to restore the inhibitory effect of SS on GH release after pre-exposure of SS (30 nM) to the pituitary cells. We conclude that SS antagonizes carp GRF on GH release at the pituitary level in rainbow trout and this antagonism is noncompetitive. SS has a postantagonism to carp GRF which may implicate some important physiological adaptations in teleosts.


ZnUMBA - a live imaging method to detect local barrier breaches.
Epithelial barrier function is commonly analyzed using transepithelial electrical resistance, which measures ion flux across a monolayer, or by adding traceable macromolecules and monitoring their passage across the monolayer. Although these methods measure changes in global barrier function, they lack the sensitivity needed to detect local or transient barrier breaches, and they do not reveal the location of barrier leaks. Therefore, we previously developed a method that we named the zinc-based ultrasensitive microscopic barrier assay (ZnUMBA), which overcomes these limitations, allowing for detection of local tight junction leaks with high spatiotemporal resolution. Here, we present expanded applications for ZnUMBA. ZnUMBA can be used in Xenopus embryos to measure the dynamics of barrier restoration and actin accumulation following laser injury. ZnUMBA can also be effectively utilized in developing zebrafish embryos as well as cultured monolayers of Madin-Darby canine kidney (MDCK) II epithelial cells. ZnUMBA is a powerful and flexible method that, with minimal optimization, can be applied to multiple systems to measure dynamic changes in barrier function with spatiotemporal precision.


[Multiparametric flow cytometry analyzes the expressions of immunophenotype CD133, CD34, CD44 in lung cancer naive cells].
To study the expression of CD133, CD34 and CD44 in lung cancer, and distribution of cell subpopulations that generated by combination of different markers. By collecting 10 normal lung tissues and 40 lung cancer fresh samples that were diagnosed pathologically, preparing single cell suspension, and labelling cells with CD133, CD34, CD44, CD117, CD43, CD45 and LIN(CD2, CD3, CD31, CD64) monoclone antibodies, we analyzed the distribution of the above-mentioned antibodies in lung cancer cells on FCM. By double-parameters plots, we analyzed the naive cell subpopulations that were generated through combination of positive and negative antigen expression. In lung cancer parenchymal-cells (LIN- CD45-) expressed CD133, CD34 and CD44 dim positive and, expressed CD117 and CD43 negative. The mann-Whitney rank test results shows that there was no significant difference for the expression of CD133, CD34, CD44 between lung cancer and normal lung tissue, and CD44+, CD133- CD34-, CD133+ CD44+, CD133+ CD44-, CD133+ CD34+, CD133- CD34+ and CD133- CD44+ expressed differently (P < 0.05) between lung adenocarcinoma and lung squamous cell carcinoma. The cluster analysis results suggest that they are classified to 4 subsets. CD133, CD34, CD44 could be the marker of lung cancer naive cells, which could contribute to study lung cancer cell development.


Functional Characterization of Three Specific Acyl-Coenzyme A Synthetases Involved in Anaerobic Cholesterol Degradation in Sterolibacterium denitrificans Chol1S.
The denitrifying betaproteobacterium Sterolibacterium denitrificans Chol1S catabolizes steroids such as cholesterol via an oxygen-independent pathway. It involves enzyme reaction sequences described for aerobic cholesterol and bile acid degradation as well as enzymes uniquely found in anaerobic steroid-degrading bacteria. Recent studies provided evidence that in S. denitrificans, the cholest-4-en-3-one intermediate is oxygen-independently oxidized to Δ4-dafachronic acid (C26-oic acid), which is subsequently activated by a substrate-specific acyl-coenzyme A (acyl-CoA) synthetase (ACS). Further degradation was suggested to proceed via unconventional β-oxidation, where aldolases, aldehyde dehydrogenases, and additional ACSs substitute for classical β-hydroxyacyl-CoA dehydrogenases and thiolases. Here, we heterologously expressed three cholesterol-induced genes that putatively code for AMP-forming ACSs and characterized two of the products as specific 3β-hydroxy-Δ5-cholenoyl-CoA (C24-oic acid)- and pregn-4-en-3-one-22-oyl-CoA (C22-oic acid)-forming ACSs, respectively. A third heterologously produced ATP-dependent ACS was inactive with C26-, C24-, or C22-oic-acids but activated 3aα-H-4α-(3'propanoate)-7aβ-methylhexahydro-1,5-indanedione (HIP) to HIP-CoA, a rather late intermediate of aerobic cholesterol degradation that still contains the CD rings of the sterane skeleton. This work provides experimental evidence that anaerobic steroid degradation proceeds via numerous alternate CoA-ester-dependent or -independent enzymatic reaction sequences as a result of aldolytic side chain and hydrolytic sterane ring C-C bond cleavages. The aldolytic side chain degradation pathway comprising highly exergonic ACSs and aldehyde dehydrogenases is considered to be essential for driving the unfavorable oxygen-independent C26 hydroxylation forward.IMPORTANCE The biological degradation of ubiquitously abundant steroids is hampered by their low solubility and the presence of two quaternary carbon atoms. The degradation of cholesterol by aerobic Actinobacteria has been studied in detail for more than 30 years and involves a number of oxygenase-dependent reactions. In contrast, much less is known about the oxygen-independent degradation of steroids in denitrifying bacteria. In the cholesterol-degrading anaerobic model organism Sterolibacterium denitrificans Chol1S, initial evidence has been obtained that steroid degradation proceeds via numerous alternate coenzyme A (CoA)-ester-dependent/independent reaction sequences. Here, we describe the heterologous expression of three highly specific and characteristic acyl-CoA synthetases, two of which play key roles in the degradation of the side chain, whereas a third one is specifically involved in the B ring degradation. The results obtained shed light into oxygen-independent steroid degradation comprising more than 40 enzymatic reactions.


Bladder endothelin-1 receptor binding of bosentan and ambrisentan.
The present study aimed to characterize bladder endothelin-1 (ET-1) receptor binding of clinically used ET-1 receptor antagonists by using [(125)I]ET-1. The inhibition of specific [(125)I]ET-1 binding was measured in the presence of ET-1 and its receptor antagonists. Specific binding of [(125)I]ET-1 in rat bladder was saturable and of high affinity, which characterized selective labeling of bladder ET-1 receptors. ET-1, bosentan, ambrisentan, and CI-1020 inhibited specific [(125)I]ET-1 binding in a concentration-dependent manner at nanomolar ranges of IC50. Nonlinear least squares regression analysis revealed the presence of high- and low-affinity ET-1 receptor sites for ambrisentan and CI-1020. Bosentan and ambrisentan significantly increased the dissociation constant for bladder [(125)I]ET-1 binding without affecting maximal number of binding sites (Bmax). Thus, bosentan and ambrisentan seem to bind to bladder ET-1 receptor in a competitive and reversible manner. Oral administration of bosentan caused a dose-dependent decrease in Bmax for bladder [(125)I]ET-1 binding, suggesting significant binding of bladder ET-1 receptors in vivo. A significant amount of pharmacologically relevant ET-1 receptors may exist in the bladder. These receptors may be implicated in the pathogenesis of lower urinary tract symptoms and may also be promising targets for the development of therapeutic agents.


[Neoplastic Vesico-vaginal Fistula (VVF) secondary to bladder cancer: a rare entity].
Vesico-vaginal Fistula (VVF) secondary to bladder cancer is extremely rare. We report the case of a 54-year old post-menopausal patient with neoplasic Vesico-vaginal Fistula (VVF), without any surgical antecedents or recent obstetric trauma. Biopsy of the edges of the fistula confirmed urothelial carcinoma. In light of this observation, we here discuss VVF etiological forms and their different therapeutic strategies.


Programming patchy particles to form three-dimensional dodecagonal quasicrystals.
Model patchy particles have been shown to be able to form a wide variety of structures, including symmetric clusters, complex crystals, and even two-dimensional quasicrystals. Here, we investigate whether we can design patchy particles that form three-dimensional quasicrystals, in particular targeting a quasicrystal with dodecagonal symmetry that is made up of stacks of two-dimensional quasicrystalline layers. We obtain two designs that are able to form such a dodecagonal quasicrystal in annealing simulations. The first is a one-component system of seven-patch particles but with wide patches that allow them to adopt both seven- and eight-coordinated environments. The second is a ternary system that contains a mixture of seven- and eight-patch particles and is likely to be more realizable in experiments, for example, using DNA origami. One interesting feature of the first system is that the resulting quasicrystals very often contain a screw dislocation.


Lymphology and translational medicine.
Lymphology is evolving in search of a better management of lymphedema patients, both as to the diagnostic pathway and as to the therapeutic options. Similarly, lymphatic system is involved in a wide spectrum of pathophysiologic processes of most chronic degenerative diseases. Translational medicine integrates the interdisciplinary scientific knowledge to improve diagnostic and therapeutic options in the biomedical field. Inflammation and lymphatic function are regarded as the connecting biochemical factors in most diseases. This review focuses on the scientific publications regarding lymphatic system in connection to psycho-neuroendocrine immunology, hormesis, epigenetics and more generally nutrition and lifestyle. The interaction between lymphology and translational medicine may play a relevant role to improve management of lymphedema on the one hand, and of chronic degenerative diseases on the other.


The effects of selected drugs, including chlorpromazine and non-steroidal anti-inflammatory agents, on polyclonal IgG synthesis and interleukin 1 production by human peripheral blood mononuclear cells in vitro.
We tested a range of drugs for their effects on in vitro polyclonal IgG synthesis by human peripheral blood mononuclear cells (PBMC) stimulated with the lectin pokeweed mitogen (PWM). The test drugs were selected on the basis of reported disruptive effects on immune function in vivo. IgG production between day 4 and days 7 or 8 of culture was measured by biotin-streptavidin sandwich ELISA. The anti-psychotic agent chlorpromazine (0.55-1.7 microM) enhanced IgG synthesis to approximately double control levels. In contrast, the non-steroidal anti-inflammatory drugs (NSAIDs) indomethacin, piroxicam, ibuprofen and aspirin inhibited IgG synthesis by up to 50%, with a rank order of potency that reflects their activity as inhibitors of cyclo-oxygenase. Phenytoin, procainamide, propylthiouracil, methimazole, D-penicillamine and D-penicillamine-L-cysteine all failed to modulate IgG synthesis at non-toxic concentrations. The potentiation and inhibition of IgG synthesis by chlorpromazine and indomethacin, respectively, was observed only when the drug was present during the first 24 h of culture. Neither chlorpromazine nor indomethacin, at non-toxic concentrations, affected PHA- and PWM-stimulated proliferation of PBMC. In addition, chlorpromazine, indomethacin and piroxicam, at concentrations which produced maximal modulation of IgG synthesis, and D-penicillamine and D-penicillamine-L-cysteine at 10 microM failed to influence production of interleukin-1-like activity. We conclude that chlorpromazine and NSAIDs, although they exert opposite effects on IgG synthesis, act at an early stage of B cell differentiation that appears to be independent of interleukin 1 synthesis and early proliferative events.


Action of theophylline on secretagogue-stimulated amylase release from dispersed pancreatic acini.
In dispersed acini from guinea pig pancreas, theophylline did not alter basal amylase release, but had three functionally distinct modes of action on the stimulation of amylase release caused by various secretagogues. 1) At relatively low concentrations (0.1-1.0 mM), theophylline augmented the increase in enzyme secretion caused by vasoactive intestinal peptide, secretin, or 8-bromoadenosine 3',5'-monophosphate, but did not alter the increase in amylase release caused by other secretagogues. 2) At intermediate concentrations (1-10 mM), theophylline selectively altered the increase in enzyme secretion caused by carbamylcholine, but did not alter the effects of cholecystokinin or bombesin, secretagogues whose modes of action are similar to that of cabamylcholine. 3) At high concentrations (greater than 10 mM), theophylline inhibited the increase in enzyme secretion caused by all secretagogues tested.


Progressive ocular inflammation following anti-tubercular therapy for presumed ocular tuberculosis in a high-endemic setting.
To analyze the incidence and clinical course of patients developing progressive ocular inflammation following anti-tubercular therapy (ATT) for presumed ocular tuberculosis (TB). Retrospective analysis of medical records of patients who received ATT for presumed ocular TB and completed at least 12 months follow-up after initiation of ATT. The diagnosis of presumed ocular TB was based on presence of ocular signs suggestive of TB, evidence of past tubercular infection, and exclusion of mimicking clinical entities. All patients received a combination of ATT and corticosteroid therapy. Primary outcome measure was progression (worsening) of ocular inflammation, defined as a two-step increase in level of inflammation (anterior chamber/ vitreous) or the appearance of new lesions following initiation of ATT. A total of 106 patients (64 male, 42 female) received ATT for presumed ocular TB. Twenty-six (24.5%) patients developed progressive intraocular inflammation following ATT. Primary diagnoses in these patients were: anterior uveitis (n=1), intermediate uveitis (n=9), retinal vasculitis (n=3), serpiginous-like choroiditis (n=7), multifocal choroiditis (n=2), and pan-uveitis (n=4). Following progressive inflammation, diagnosis was revised in two patients (7.7%)-both responded to alternative therapy. Of the rest, majority (n=16; 61.5%) resolved with escalation of corticosteroid therapy. Five patients (19.2%)-all having intermediate uveitis-required therapeutic vitrectomy for resolution. Three patients (11.5%) had persistent inflammation at end of follow-up period. Progressive inflammation following ATT for presumed ocular TB is common. It generally resolves on escalation of corticosteroid therapy. Cases not responding to increased immunosuppression need to be re-investigated to rule out a nontubercular cause.


Hepatocellular carcinoma associated with second primary malignancy.
In a consecutive series of 562 patients with pathologically documented hepatocellular carcinoma (HCC), 12 patients (2.1%) were found to have a second primary malignancy elsewhere. Of these, eight were male, four female, with ages ranging from 49 to 76 years (mean 60.7 +/- 9.3 years). The associated cancers included eight cases of gastric cancers, an esophageal cancer, a stump cancer, a case of myelocytic leukemia and a histiocytic lymphoma. Eight cases had both malignancies diagnosed at the same admission. In the other four, HCC were detected after an interval of 4, 10, 12 and 39 months. Two had received previous chemotherapy or radiotherapy. Fifty percent of the 12 patients were hepatitis B surface antigen (HBsAg) positive. Their liver function tests and alpha-fetoprotein levels were consistent with those of patients with HCC alone. The results suggest that the occurrence of HCC concomitant with or arising after another primary malignancy in Taiwan is not rare.


Green Synthesis and the Evaluation of a Functional Amphiphilic Block Copolymer as a Micellar Curcumin Delivery System.
Polymer micelles represent one of the most attractive drug delivery systems due to their design flexibility based on a variety of macromolecular synthetic methods. The environmentally safe chemistry in which the use or generation of hazardous materials is minimized has an increasing impact on polymer-based drug delivery nanosystems. In this work, a solvent-free green synthetic procedure was applied for the preparation of an amphiphilic diblock copolymer consisting of biodegradable hydrophobic poly(acetylene-functional carbonate) and biocompatible hydrophilic polyethylene glycol (PEG) blocks. The cyclic functional carbonate monomer 5-methyl-5-propargyloxycarbonyl-1,3-dioxane-2-one (MPC) was polymerized in bulk using methoxy PEG-5K as a macroinitiator by applying the metal-free organocatalyzed controlled ring-opening polymerization at a relatively low temperature of 60 °C. The functional amphiphilic block copolymer self-associated in aqueous media into stable micelles with an average diameter of 44 nm. The copolymer micelles were physico-chemically characterized and loaded with the plant-derived anticancer drug curcumin. Preliminary in vitro evaluations indicate that the functional copolymer micelles are non-toxic and promising candidates for further investigation as nanocarriers for biomedical applications.


Presynaptic modulation of synaptic transmission by opioid receptor in rat subthalamic nucleus in vitro.
Presynaptic modulation of synaptic transmission in rat subthalamic nucleus (STN) neurons was investigated using whole-cell patch-clamp recordings in brain slices. Evoked GABAergic inhibitory postsynaptic currents (IPSCs) were reversibly reduced by methionine enkephalin (ME) with an IC(50) value of 1.1 +/- 0.3 microM. The action of ME was mimicked by the mu-selective agonist [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO), and was partially blocked by the mu-selective antagonists naloxonazine and D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP). Evoked GABA(A) IPSCs were also inhibited by the delta-selective agonist [D-Pen(2,5)]-enkephalin (DPDPE), but not by the kappa-selective agonist (+)-(5 alpha,7 alpha,8 beta)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-benzeneacetamide (U-69593) and the orphan receptor agonist orphanin FQ/nociceptin (OFQ). DPDPE-induced inhibition was completely blocked by the delta-selective antagonist N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI 174,864). ME, DAMGO and DPDPE increased the paired-pulse ratio of IPSCs. Evoked excitatory postsynaptic currents (EPSCs) were reversibly reduced by ME with an IC(50) value of 0.35 +/- 0.14 microM. Inhibition by ME was associated with an increase in the paired-pulse ratio of EPSCs. The action of ME was mimicked by DAMGO, and blocked by naloxonazine. DPDPE had little effect on evoked EPSCs. Neither U-69593 nor OFQ had any effect. ME significantly decreased the frequency of spontaneous miniature EPSCs (mEPSCs) without change in their amplitude. The action of ME was mimicked by DAMGO. DPDPE had no effect. The presynaptic voltage-dependent potassium conductance blocker 4-aminopyridine (4-AP, 100 microM) abolished the inhibitory effects of ME on evoked IPSCs and EPSCs. In contrast, 4-AP only partially blocked the actions of baclofen. These results suggest that opioids inhibit inhibitory synaptic transmission in the STN through the activation of presynaptic mu- and delta- receptors. In contrast, inhibition of excitatory synaptic inputs to the STN occurs through the activation of only mu-receptors. Both inhibitions may be mediated by blockade of voltage-dependent potassium conductance.


Cardiomyocyte precursors and telocytes in epicardial stem cell niche: electron microscope images.
A highly heterogeneous population of stem and progenitor cells has been described by light immunohistochemistry in the mammalian adult heart, but the ultrastructural identity of cardiac stem cells remains unknown. Using electron microscopy, we demonstrate the presence of cells with stem features in the adult mouse heart. These putative cardiac stem cells are small (6-10 microm), round cells, with an irregular shaped nucleus, large nucleolus, few endoplasmic reticulum cisternae and mitochondria, but numerous ribosomes. Stem cells located in the epicardial stem cell niche undergo mitosis and apoptosis. Cells with intermediate features between stem cells and cardiomyocyte progenitors have also been seen. Moreover, electron microscopy showed that cardiomyocyte progenitors were added to the peripheral working cardiomyocytes. Telocytes make a supportive interstitial network for stem cells and progenitors in the stem cell niche. This study enhances the hypothesis of a unique type of cardiac stem cell and progenitors in different stages of differentiation. In our opinion, stem cells, cardiomyocyte progenitors and telocytes sustain a continuous cardiac renewal process in the adult mammalian heart.


How to plan, deliver and evaluate a training session.
The long term aim of general practice teaching is to train competent general practitioners to provide high quality care to patients in any setting. The Royal Australian College of General Practitioners' (RACGP) curriculum sets educational outcomes for postgraduate general practice training programs throughout Australia. Registrars have input to this process by reflecting on their learning needs and developing learning plans. This article discusses the teaching of practical procedures in general practice and describes the planning, delivery and evaluation of an educational session about the management of shoulder conditions for general practice registrars.


Ventricular volume regulation: a mathematical model and computer simulation.
A mathematical model of ventricular volume regulation based on fluid mechanical principles has been constructed using a systems engineering approach. The parameters used in the model are based on clinical observation, laboratory investigation, and presumptions that will be tested later. The model was constructed to be the basis of a computer simulation. Using the computer simulation, information obtained from the literature and laboratory hypotheses regarding pathophysiology, several enigmatic conditions were tested. The model predicted that over-production of cerebrospinal fluid, as in the case of choroid plexus papilloma, could by itself lead to distention of the ventricular system. In simulating pseudotumor cerebri, if cerebrospinal fluid absorption at the arachnoid villi is impaired and the brain itself is rendered incompressible by swelling, intracranial pressure rises and ventricular volume diminishes. Conversely, in normal-pressure hydrocephalus, if cerebrospinal fluid flow is restricted between the spinal and cortical subarachnoid spaces and the brain is made more compressible, the ventricular volume increases with minimal increases in intracranial pressure. This mathematical model and its associated computer simulation is useful in predicting the behavior of the volume of the cerebral ventricles to a variety of pathological phenomena.